This disclosure relates generally to an apparatus and method for an improved calorimeter, and more specifically, to a system and method for an improved calorimeter for measuring the heat released or absorbed during chemical reactions.
Screening campaigns, including high-throughput screening (HTS) campaigns, typically rely on assays using library compounds (e.g., labeled ligands or enzyme substrates. Artifacts associated with labeling have led to erroneous identification of active compounds.
HTS campaigns have historically relied on binding assays using labeled (fluorescent, radioactive) reporter constructs or enzymatic assays using labeled substrates. The attachment of fluorescent tags or development of fluorescent substrates requires additional assay development work and these modifications of the ligand or substrate can sometimes have adverse effects on binding/catalysis, leading to false positives and false negatives.
Calorimetry is the measurement of the quantity of heat evolved or absorbed in various processes (e.g., chemical reactions, changes of state, and formation of solutions). Calorimetry is a powerful technique for characterizing biochemical interactions, including enzymatic reactions, ligand binding, and organelle and cellular activity. It does not require labeling or immobilization of reagents. However, conventional calorimeters are limited by large sample requirements and low throughput. Accordingly, the use of calorimetry is relegated to a limited number of high-value measurements.
It would be desirable to develop new systems and methods for screening active compounds that utilize smaller samples, permit greater throughput, and avoid the problems associated with labeling.